Influência do cloridrato de pioglitazona na regulação da resposta inflamatória de pacientes com Leishmaniose cutânea causada por l. braziliensis

Abstract

Cutaneous leishmaniasis (CL) caused by Leishmania braziliensis is an inflammatory disease 12 in which the development of skin ulcers is associated with the presence of mononuclear cells 13 and high levels of inflammatory cytokines. Recently was demonstrated that activation of 14 PPAR-γ by anti-diabetic drugs decreased cytokine production in many types of inflammatory 15 diseases. We hypothesized that activation of PPAR-γ by pioglitazone hydrochloride could 16 regulate the inflammatory response observed in CL. In this article, we show that pioglitazone 17 hydrochloride at different concentrations downregulated TNF, IL-6, IL-1β and IL-10 produc-18 tion after TLR4 activation in monocytes of healthy subjects. However, we have shown that 19 peripheral blood mononuclear cells from Leishmania antigen-stimulated CL patients had de-20 creased TNF levels after treatment with this drug at a low concentration for a short time of 21 stimulation. This observed immunomodulatory effect, was modified by exposing these cells to 22 a higher concentration of pioglitazone hydrochloride for a longer time. In addition, macro-23 phages infected with L. braziliensis showed reduced parasitic load when treated this drug. 24 These results suggest that pioglitazone hydrochloride in low concentration may have benefits 25 in adjuvant CL therapy.